AB0968 RAPID ONSET OF EFFICACY IN CHINESE PATIENTS WITH ACTIVE RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS TREATED WITH IXEKIZUMAB: A PHASE 3 STUDY
Authors: Y. Xue, J. Hu, D. Liu, J. Li, H. Wu, C. Tan, L. Dai, Y. Yan, H. Li, H. Zou
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, has demonstrated efficacy in global clinical trials in patients with active radiographic axial spondyloarthritis (r-axSpA)/ankylosing spondylitis (AS) <sup>[1,2]</sup>. Rapid onset of clinical improvement is one of the most important needs of treatment for r-axSpA patients. <h3>Objectives</h3> To evaluate the onset time of ixekizumab in Chinese patients with r-axSpA. <h3>Methods</h3> This report evaluated efficacy onset time of r-axSpA patients treated with ixekizumab compared with placebo based on data from a phase 3 study in China. The major secondary efficacy measures in this report included Assessment of Spondyloarthritis International Society (ASAS) 40 response, ASAS 20 response, change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS), change from baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), and ASDAS &lt;2.1 response. Other secondary efficacy measures in this report included change from baseline of ASAS individual components (like patient global, Spinal pain, Inflammation, high sensitivity C-reactive protein [hsCRP]), proportion of patients who experience clinically important improvement (change of ASDAS from baseline ≥1.1), major improvement (change of ASDAS from baseline ≥2.0), and BASDAI 50 response. All efficacy measures were evaluated from week 0 through week 52. A logistic regression model and mixed-effects model of repeated measures (MMRM) were used to analyze categorical and continuous measures from week 0 to 16 (placebo-controlled period), and categorical missing data were imputed using non-responder imputation (NRI). <h3>Results</h3> More patients achieved ASAS40 and ASAS20 response as early as week 1 (p = 0.042 and p &lt; 0.001) in the ixekizumab-treated group compared with placebo. In addition, statistically significant (p &lt; 0.05) improvements were observed as early as week 1 for the ixekizumab group compared to placebo in almost all efficacy measures mentioned above. For other outcomes including proportion of patients who experience major improvement and BASDAI 50 response, differences were evident (p &lt; 0.05) by week 2 in the ixekizumab group compared with placebo. Furthermore, ixekizumab sustained high efficacy in all efficacy measures through 52 weeks. <h3>Conclusion</h3> Ixekizumab demonstrated a rapid onset of efficacy improvements on ASAS response, ASAS core set values, disease activity and function in Chinese patients with r-axSpA. <h3>References</h3> [1]Désirée van der Heijde, James Cheng-Chung Wei, Maxime Dougados, et al. Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-controlled trial. <i>Lancet</i> 2018; 392: 2441–51. [2]Deodhar A, Poddubnyy D, Pacheco-Tena C, et al. Efficacy and safety of ixekizumab in the treatment of radiographic axial spondyloarthritis: sixteen-week results from a phase III randomized, double-blind, placebo-controlled trial in patients with prior inadequate response to or intolerance of tumor necrosis factor inhibitors. <i>Arthritis Rheumatol</i> 2019; 71:599–611. <h3>Acknowledgements</h3> The author would like to thank Zipei Xiao for medical assistance and Fei Ji for peer review (both of Eli Lilly and Company employees), and all study participants. <h3>Disclosure of Interests</h3> YU XUE Consultant of: Yu Xue has been investigator of Eli Lilly and Company, Jiankang Hu Consultant of: Jiankang Hu has been investigator of Eli Lilly and Company, Dongzhou Liu Consultant of: DongZhou Liu has been investigator of Eli Lilly and Company, Jingyang Li Consultant of: Jingyang Li has been investigator of Eli Lilly and Company, Huaxiang Wu Consultant of: Huaxiang Wu has been investigator of Eli Lilly and Company, Chunyu Tan Consultant of: Chunyu Tan has been investigator of Eli Lilly and Company, Lie Dai Consultant of: Lie Dai has been investigator of Eli Lilly and Company, Yan Yan Employee of: Yan Yan is employee of Eli Lilly and Company, Hongying Li Shareholder of: HongYing Li is minor stockholder of Eli lilly and Company, Employee of: HongYing Li is employee of Eli Lilly and Company, Hejian Zou Consultant of: Hejian Zou has been investigator of Eli Lilly and Company.